Research reportERK-dependent brain-derived neurotrophic factor regulation by hesperidin in mice exposed to chronic mild stress

•Hesperidin produces antidepressant-effects in behavioral tests.•Hesperidin promotes ERK phosphorylation and BDNF expression in the hippocampus.•ERK inhibitor SL327 abolishes the effects of hesperidin.

A previous study found that the antidepressant-like effects of ethanolic extracts from Hemerocallis citrina are predominantly related to the flavonoid, hesperidin. The study herein aimed to explore the antidepressant-like mechanism of hesperidin in mice induced by chronic mild stress (CMS). The results indicated that hesperidin reversed the reduction of sucrose preference and the elevation of immobility time in mice induced by CMS. In addition, the increase in serum corticosterone levels and decrease in hippocampal extracellular signal-regulated kinase (ERK) phosphorylation and brain-derived neurotrophic factor (BDNF) levels in CMS mice were also ameliorated by hesperidin treatment. In contrast, improvement by hesperidin was suppressed by pretreatment with ERK inhibitor SL327. Taken together, our findings confirmed the antidepressant-like effect of hesperidin and indicated that hesperidin-induced BDNF up-regulation was mediated in an ERK-dependent manner.